Metabolism monooxygenase-catalyzed

Humphreys, J. M. Hemm, M. R. Chappie, C. Ferulate 5-hydroxylase fromArahidopsis is a multifunctional cytochrome P450-dependent monooxygenase catalyzing parallel hydroxylations in phenylpropanoid metabolism. Proc. Natl. Acad Sci. USA 1999, 96, 10045-10050. 

Natural (-)-cocaine (7.57, Fig. 7.8), which has the (2/ ,3S)-configuration, is a relatively poor substrate for hepatic carboxylesterases and plasma cholinesterase (EC 3.1.1.8), and also a potent competitive inhibitor of the latter enzyme [116][121], In contrast, the unnatural enantiomer, (+)-(2S,3/ )-cocaine, is a good substrate for carboxylesterases and cholinesterase. Because hydrolysis is a route of detoxification for cocaine and its stereoisomers, such metabolic differences have a major import on their monooxygenase-catalyzed toxification, a reaction of particular effectiveness for (-)-cocaine. 

Chemical Mechanisms of the Cytochrome P-450 Monooxygenase-Catalyzed Metabolism of Phosphorothionate Triesters... 

Parathion is also metabolized to diethyl phosphorothioic acid and -nitrophenol in a reaction requiring a cytochrome P-4Jg-containing monooxygenase enzyme system (, 4). Studies with H. 0 have indicated that water in addition to molecular oxygen and NADPH is required in this reaction ( ). Diethyl phosphate and -nitro-phenol can also be formed from parathion in a monooxygenase-catalyzed reaction (6). 

Contents Low-molecular-weight organosulfur compounds in nature / Eric Block—Chemical mechanisms of the cytochrome P-450 monooxygenase-catalyzed metabolism of phosphorothionate triesters / R. A. Neal —Sulfur in propesticide action / T. R. Fukuto and M. A. H. Fahmy—[etc.]... 

For sulfoxides/sulfides, oxidation is catalyzed by cytochrome P-450 and flavin monooxygenases, whereas the reductive metabolism is catalyzed by aldehyde oxidase and/or thiotedocin-linked enzymes. The fiver as well as the gut and bacterial flora are potential sites for the formation of sulfide metabolites. 

St-Pierre B, De Luca V (1995) A cytochrome P-450 monooxygenase catalyzes the first step in the conversion of tabersonine to vindoline in Catharanthus roseus. Plant Physiol 109 131-139 Stafford HA (1990) Flavonoid metabolism. CRC Press, Boca Raton, FL... 

PAHs can be bioconcentrated or bioaccumulated by certain aquatic invertebrates low in the food chain that lack the capacity for effective biotransformation (Walker and Livingstone 1992). Mollusks and Daphnia spp. are examples of organisms that readily bioconcentrate PAH. On the other hand, fish and other aquatic vertebrates readily biotransform PAH so, biomagnification does not extend up the food chain as it does in the case of persistent polychlorinated compounds. As noted earlier, P450-based monooxygenases are not well represented in mollusks and many other aquatic invertebrates (see Chapter 4, Section 4.2) so, this observation is not surprising. Oxidation catalyzed by P450 is the principal (perhaps the only) effective mechanism of primary metabolism of PAH. 

Xenobiotics are metabolized in two phases. The major reaction of phase 1 is hydroxylation catalyzed by a variety of monooxygenases, also known as the cytochrome P450s. In phase 2, the hydroxylated species are conjugated with a variety of hydrophihc compounds such as glucuronic acid, sulfate, or glutathione. The combined operation of these two phases renders lipophilic compounds into water-soluble compounds that can be ehminated from the body. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Methanotrophs rely on the enzymatic system methane monooxygenase (MMO) to catalyze the first step in the metabolism of methane, shown in Eq. (1) (1, 14). 

In some cases, microorganisms can transform a contaminant, but they are not able to use this compound as a source of energy or carbon. This biotransformation is often called co-metabolism. In co-metabolism, the transformation of the compound is an incidental reaction catalyzed by enzymes, which are involved in the normal microbial metabolism.33 A well-known example of co-metabolism is the degradation of (TCE) by methanotrophic bacteria, a group of bacteria that use methane as their source of carbon and energy. When metabolizing methane, methanotrophs produce the enzyme methane monooxygenase, which catalyzes the oxidation of TCE and other chlorinated aliphatics under aerobic conditions.34 In addition to methane, toluene and phenol have been used as primary substrates to stimulate the aerobic co-metabolism of chlorinated solvents. 

The water molecule, either as a reactant or a product, plays an important role in the metabolism of innumerable endogenous and exogenous compounds. Water is, of course, a by-product of some metabolic redox reactions, e.g., reactions catalyzed by monooxygenases [7], However, this book focuses on non-redox reactions involving water as a reactant or a product. 

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